Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Codeine”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,315 records · Page 73Linked to original sources

[Social psychiatric study of the over-the-counter antitussive drug abuse; shifts resulting from modification of the formulae].

We surveyed 22 patients (of whom 4 were women) with a history of antitussive drug abuse at a psychiatric hospital in the suburbs of Tokyo and at the Clinical Institute for Addiction Problems from 1 July 1986 to 30 June 1991. for changes in their pattern of abuse after the composition was altered. Here are our findings: 1) Researchers have long differed on whether ephedrine or codeine was responsible for the abuse of over-the-counter antitussive agents. The present study revealed that although codeine was still present in the new Bron syrup, its abuse was clearly on the decline in Japan, leading us therefore to conclude that psychological dependence on ephedrine was central to the spate of over-the-counter antitussive abuse observed in the 1980s. Although we cannot ignore the mellow feeling codeine creates, it is difficult to give it more central role in the abuse of such drugs. 2) Users were divided into two groups, one that had used other agents before using antitussives, and another that had never used any other agent but antitussives. A comparison of these two groups revealed clear differences in learning behavior, social adaptation, familial environment and delinquent tendencies, prior to their drug abuse. 3) After the composition was altered, abuse spread to Tonin syrup manufactured by another laboratory, Bron tablets, new Bron syrup and ephedrine tablets. Relatively recently, there have been some new cases of abuse of Bron tablets and an increase in the number of cases who continued to use Bron syrup even after its composition was altered. The Medical literature also reveals that in many countries the abuse of both codeine and ephedrine is becoming a social problem, and clearly either agent may be abused separately.

Adolescent↗

Opioid use by patients in an orthopedics spine clinic.

OBJECTIVE: Concerns regarding the efficacy, toxicity, tolerance, dependence, and abuse of opioids have limited their use for patients with chronic spine pain. In our previous study of rheumatology clinic patients, opioid analgesics were found to be highly effective, produced only mild side effects, and had few instances of opioid abuse. The purpose of this study was to replicate our previous study in another large cohort of patients with nonmalignant pain due to well-defined spinal diseases. METHODS: Opioid use was studied in 230 orthopedics spine clinic patients by retrospective analysis of prescriptions for 3 years and cross-sectional analysis of efficacy and toxicity by patient interviews. Opioid use and stability of the daily dose over 3 years were derived from computerized pharmacy records. Medical records, operative reports, and radiographic studies were reviewed to determine the reason for dosage escalations and to detect instances of abuse or addiction behaviors. Patients were interviewed to determine the efficacy, frequency, and types of side effects and instances of obtaining opioids from sources outside the Veterans Affairs system. RESULTS: Opioids were prescribed for 152 of the 230 patients, for < 3 months (short-term [STO]) in 94, > or =3 months (long-term [LTO]) in 58, and none in 72 (no opioid [NTO]). Medications prescribed were codeine, oxycodone, propoxyphene, tramadol, morphine, meperidine, fentanyl, or hydroxycodone, either alone or in combination. Interviews were completed in 72 STO, 50 LTO, and 45 NTO patients. Pain severity (0-10 scale) was not different in patients with different spinal pathologies. Opioids significantly reduced the back pain severity score from 8.3 +/- 1.5 to 4.5 +/- 2.2 (mean +/- SD). Mild side effects (most commonly, constipation and sedation) were reported by 58% of the opioid-treated patients but rarely caused them to stop taking the medication. There was no significant increase from the mean +/- SD initial opioid dosage of 5.0 +/- 12.2 30-mg codeine equivalents per day (30 mg oral codeine = 5 mg oral morphine) to the mean peak dosage of 7.9 +/- 12.5 and the mean recent dosage of 4.3 +/- 6.3, suggesting that tolerance to opioid analgesia did not appear to occur in these patients. Dosage escalations of > 2 30-mg codeine equivalents occurred 19 times in 17 LTO patients and was due to worsening of the underlying painful condition, complications of spine surgery, or unrelated surgical or medical problems in all but 3 of them (5%). These 3 patients also displayed other abuse behaviors. Abuse behaviors were not more frequent in those with or without a history of abuse/addiction. CONCLUSION: This study provides data on the efficacy, toxicity, tolerance, and abuse or addiction behaviors with opioid therapy in a large cohort of patients in an orthopedics spine clinic. The results provide objective data from patients with well-defined spine diagnoses to challenge the position that opioid treatment is inappropriate for chronic nonmalignant pain. This study provides clinical evidence to support and protect physicians treating patients with chronic musculoskeletal diseases, who may be reluctant to prescribe opioids because of possible sanctions from regulatory agencies. More important, it will benefit patients by permitting them to receive these effective, safe medications.

Aged↗

Analgesic efficacy of ketoprofen in postpartum, general surgery, and chronic cancer pain.

This article summarizes the results of five single-dose clinical studies of three pain models: postpartum, postoperative, and chronic cancer pain. The efficacy of ketoprofen (in varying doses from 25 to 225 mg) was compared with one of the following standards: aspirin (650 mg), codeine (90 mg), acetaminophen (650 mg) plus codeine (60 mg), and parenteral morphine (5 mg and 10 mg). The results indicate that ketoprofen in doses as low as 25 mg has analgesic properties significantly superior to those of placebo. For the treatment of postpartum pain, ketoprofen was significantly more effective than aspirin 650 mg but not significantly different from codeine 90 mg. Ketoprofen doses of 50 mg and 150 mg also provided analgesia superior to that with acetaminophen 650 mg plus codeine 60 mg for the management of moderate to severe postoperative pain. Moreover, oral doses of ketoprofen (75 and 225 mg) provided analgesia similar to that obtained with 5 and 10 mg parenteral doses of morphine. Adverse effects related to ketoprofen were relatively minor and infrequent. Ketoprofen was recently approved for use as an analgesic for treatment of mild to moderate pain in total daily doses up to 300 mg; the recommended initial dose is 25 to 50 mg every 6 to 8 hours as necessary.

Female↗

Assessment of physical dependence-inducing capacity of narcotic agonists and antagonists in rats by intermittent infusion technique.

Narcotics and other drugs were injected into the rat once an hour for about 1 week. Morphine and codeine showed physical dependency with a maintenance dose as low as 9.6 mg/kg/day. Development of dependence was also recorded in rats treated with cyclazocine (9.6 mg/kg/day) and pentazocine (96 mg/kg/day), and suspected in the levallorphan-treated (9.6 mg/kg/day) rats. Dependence on pethidine, which is known to be difficult to detect by the usual method in rats, also developed in this experiment (96 mg/kg/day), but it was estimated to be of lesser degree than that of codeine. Dependence on allazocine (9.6 mg/kg/day) and aminopyrine (96 mg/kg/day) did not develop. Barbital dependence (96 mg/dg/day) was induced, but it was distinguished from morphine-like drugs by the naloxone precipitation test and by substitution experiments. Cross-dependence between morphine and dependence-inducing drugs was investigated. Withdrawal weight loss in the morphine-dependent rats was suppressed or attenuated by pentazocine, pethidine, and codeine. Withdrawal weight loss in the rats dependent on cyclazocine, pentazocine, pethidine, or codeine was suppressed by morphine. Intermittent infusion of pentazocine at longer intervals induced dependence not as severe as that induced by 1-h infusion.

Animals↗

Prescribing patterns for analgesics in relation to underprivileged area (UPA) score, mortality and suicide in 33 municipalities in the province of Skåne, southern Sweden.

BACKGROUND: Although it is well known that analgesics contribute to suicide, there is little knowledge about how much of the mortality and suicide can be explained by socioeconomic deprivation or by sales of analgesics. METHODS: This ecological study analyses the relationships between the sales (defined daily doses per 1000 inhabitants per day) of dextropropoxyphene, dextropropoxyphene combinations, paracetamol, codeine and paracetamol combinations, and other codeine combinations and the Swedish UPA (underprivileged area) score, mortality and suicide rates in 33 municipalities in Skåne in 1987 and 1994 for people aged 20-64 years. The association of each of the subgroups of analgesics with all-cause mortality, and with standardised mortality rates for suicide, adjusted for UPA score, was investigated by using weighted (by population size) regression analysis. RESULTS: In 1994 there was a moderate to strong significant correlation between sales of analgesics and UPA scores, mortality and suicide (r = 0.49-0.78). Although UPA score explained 68.9% and 67.4% respectively of the variance between the analgesics and all-cause mortality and suicide, codeine and paracetamol combinations explained a further 10.1% of the variance in suicide. Dextropropoxyphene and codeine and paracetamol combinations explained an additional 3.8% and 2.9% respectively of the variance in mortality. CONCLUSIONS: Local prescription rates for analgesics were associated with mortality and suicide, when adjusted for socioeconomic deprivation defined as UPA score.

Adult↗

Experimental studies of the abuse potential of d, l-glaucine. 1.5-phosphate in rhesus monkeys.

d-Glaucine is an alkaloid derived from Glaucium flavum, which is as effective as codeine as an antitussive. d, l-Glaucine. 1.5 phosphate is a synthetic compound related to d-glaucine. The ability of d, l-glaucine.1.5 phosphate to maintain responding in rhesus monkeys was assessed in 2 procedures. In the first responding was maintained under a fixed-ratio 10 schedule of codeine delivery during daily 3-hr sessions. When d, l-glaucine.1.5 phosphate (0.05-0.4 mg/kg) was substituted for codeine, responding was not maintained. In the second procedure, monkeys given 23-hr/day access to 0.5-1.0 mg/kg under a fixed-ratio schedule did not self-administer d,l-glaucine.1.5 phosphate above saline levels even after a 21-day period of programmed injections. Following the period of programmed injections, there were not signs of opiate withdrawal following the administration of naloxone. These results indicate that the abuse potential of d,l-glaucine.1.5 phosphate is low relative to codeine.

Animals↗

Hyper-releasability of mast cells in family members of infants with sudden infant death syndrome and apparent life-threatening events.

BACKGROUND: An allergic reaction with increased degranulation of mast cells has been suggested as a possible mechanism in sudden infant death syndrome (SIDS). STUDY DESIGN: Mast cell releasability was assessed in 2 study groups: A, 22 subjects, 16 first-degree relatives of infants who had had an apparent life-threatening event (ALTE) and 6 infants after ALTE and B, 46 first-degree relatives of SIDS cases. These groups were compared with 71 members of an age-matched control group. In each subject the skin wheal and flare reactions were measured after an intradermal injection of 0.02 mL of each of the following substances dissolved in phenol-saline solution: histamine 0.0001 mg/mL, histamine 0.001 mg/mL, codeine 0.5 mg/mL, codeine 1 mg/mL, compound 48/80 0.05 mg/mL, compound 48/80 0. 1 mg/mL, and phenol-saline solution. The size of wheal and flare skin reaction was assessed by computerized planimetry after the shape of the cutaneous response was copied onto a paper. RESULTS: The wheal and flare skin reaction to each of the substances was significantly larger in the 2 study groups compared with the control group (P <.05) except for the wheal reaction to compound 48/80 0.1 mg/mL, codeine 0.5 mg/mL, and histamine in both concentrations for group A and the wheal reaction to codeine 1 mg/mL and histamine in both concentrations for group B. All individuals with increased reaction belonged to 3 (50%) of 6 families with ALTE history and to 8 (73%) of 11 families with SIDS history. CONCLUSIONS: Increased mast cell hyper-releasability and degranulation take place in family members of some SIDS and ALTE cases and in some infants with ALTE, supporting a possible role for an immunologic mechanism in the pathophysiology of these entities.

Adult↗

Platelet-activating factor induces histamine release from human skin mast cells in vivo, which is reduced by local nerve blockade.

BACKGROUND: Intradermal injection of platelet-activating factor (PAF) causes wheal and flare reactions, which are inhibited by antihistamines. However, PAF does not release histamine from human dispersed skin mast cells in vitro. The purpose of this study was to investigate the extent and possible mechanisms of PAF-induced histamine release in human skin in vivo with the use of dermal microdialysis. METHODS: Hollow dialysis fibers were inserted into the upper dermis in forearm skin and each fiber was perfused with Krebs-Ringer bicarbonate solution at a rate of 3.0 microliters/min. PAF (4.5 to 36 mumol/L), lyso-PAF (36 mumol/L), vehicle (negative control), and codeine 750 or 250 mumol/L (positive control) were injected intradermally above separate fibers. Dialysate was collected in 2-minute fractions for 20 minutes and histamine analyzed spectrofluorometrically. RESULTS: PAF, but not lyso-PAF, caused statistically significant dose-related histamine release and wheal and flare reactions. Intradermal mepivacaine administration significantly abrogated flare reactions by PAF and codeine and inhibited histamine release and wheal reactions by PAF but not by codeine. Long-term topical capsaicin administration inhibited histamine release and wheal reactions by PAF but not by codeine. It inhibited flare reactions induced by both compounds. PAF did not release histamine from blood basophils. CONCLUSIONS: These data suggest that PAF induced histamine release from mast cells in intact human skin indirectly via neurogenic activation. Further, on the intradermal injection of PAF histamine release and the skin responses, the wheal and the flare, are differentially regulated by neurogenic components.

Adult↗

Time of drug elimination in chronic drug abusers. Case study of 52 patients in a "low-step" detoxification ward.

The elimination time of illicit drugs and their metabolites is of both clinical and forensic interest. In order to determine the elimination time for various drugs and their metabolites we recruited 52 volunteers in a protected, low-step detoxification program. Blood samples were taken from each volunteer for the first 7 days, daily, urine sample for the first 3 weeks, daily. Urine was analyzed using a fluorescence-polarization immunoassay (FPIA) and gas chromatography/mass spectrometry (GC/MS), serum using GC/MS. The elimination times of the drugs and/or their metabolites in urine and serum as well as the tolerance intervals/confidence intervals were determined. Due to the sometimes extremely high initial concentrations and low cut-off values, a few of the volunteers had markedly longer elimination times than those described in the literature. The cut-off values were as follows: barbiturates II (200ng/ml), cannabinoids (20ng/ml), cocaine metabolites (300ng/ml), opiates (200ng/ml). GC/MS detected the following maximum elimination times: total morphine in urine up to 270.3h, total morphine and free morphine in serum up to 121.3h, monoacetylmorphine in urine up to 34.5h, 11-nor-9-carboxy-delta-9-tetrahydrocannabinol (THC-COOH) in urine up to 433.5h, THC-COOH in serum up to 74.3h, total codeine in urine up to 123h, free codeine in urine up to 97.5h, total codeine in serum up to 29h, free codeine in serum up to 6.3h, total dihydrocodeine (DHC) in urine up to 314.8h, free DHC in urine up to 273.3h, total and free DHC in serum up to 50.1h. Cocaine and its metabolites were largely undetectable in the present study.

Adult↗

Determination of opiates in hair. Effects of extraction methods on recovery and on stability of analytes.

In order to evaluate (i) the recovery of extraction of opiates from authentic hair samples and (ii) the extent of hydrolysis of acetylated opiates (6-acetylmorphine, acetylcodeine) occurring during sample preparation, three different methods of extraction commonly used for opiates have been compared. To this purpose a sample consisting of a pool of hair collected from several heroin overdose cases has been submitted alternately to (A) digestion in 2 M NaOH at 80 degrees C for 1 h (n = 5), (B) incubation in 0.1 M HCl at 45 degrees C for 18 h (n = 5) and (C) incubation in methanol at 37 degrees C for 18 h (n = 5). After pH adjustment of the different incubation media to 7-8, analytes have been isolated by means of SPE using Bond Elut certify columns and derivatized with MSTFA. Analyses have been performed by either GC-MS in the selected ion monitoring mode or, omitting SPE, by radioimmunoassay. The extent of hydrolysis of 6-acetylmorphine to morphine and of acetylcodeine to codeine have been determined by submitting blank hair samples spiked with the acetylated analytes to the different extraction methods and measuring the amount of morphine and codeine formed. Both the recovery of extraction of the total morphine fraction (6-acetylmorphine + morphine) and the rate of hydrolysis of 6-acetylmorphine were found to be in the order: A > B > C. Similar results were obtained for the total codeine fraction (acetylcodeine + codeine). These results clearly indicate that: (i) the concentration of opiates measured in hair depends on the extraction method used; (ii) ratios between different analytes (e.g. 6-acetylmorphine vs. morphine) may reflect the rate of hydrolysis during sample preparation rather than different types of exposure to opiates.

Gas Chromatography-Mass Spectrometry↗

Upside assay sensitivity in a dental pain model.

The extent of surgical trauma was related to postoperative pain intensity in a previous study. However, more extensive surgical procedures with higher baseline pain intensity did not appear to influence the ability to document the additive analgesic effect of codeine when given with paracetamol, partly due to large interindividual variation in baseline pain intensity. The aim of the present study was to attempt to improve upside assay sensitivity in this dental pain model by: (1) selecting patients with high baseline pain intensity; and (2) closer supervision of outpatients>> drug intake and compliance with protocol. Only patients with baseline pain >/=50 on a 100 mm visual analogue scale after wisdom tooth surgery were included. Twenty patients were given paracetamol 1000 mg with or without codeine 60 mg in repeated doses in a randomized and double-blind manner. Intake of the first dose of test medication and its effects were closely supervised, while the two following doses were taken at 3-h intervals after the patient had left the clinic. Pain intensity was measured with the visual analogue scale for 8 h. More pain relief was revealed when codeine 60 mg was added to paracetamol 1000 mg on the following measures of effect: change of pain intensity with time (p<0.05, Mann-Whitney), sum of pain intensities (p=0.019), pain intensity difference (p</=0.05), sum of pain intensity differences (p<0.05), pain reduction index (p<0.05) and global-evaluation score (p=0.006). The study confirms that this dental pain model, when controlled for sufficient and homogeneous baseline pain and patient compliance, does have sufficient upside assay sensitivity to discriminate between paracetamol with and without codeine. Copyright 1998 European Federation of Chapters of the International Association for the Study of Pain.

Journal Article↗

A model for human cytochrome P450 2D6 based on homology modeling and NMR studies of substrate binding.

The cytochrome P450 responsible for the debrisoquine/sparteine polymorphism (P450 2D6) has been produced in large quantities by expression of a modified cDNA in baculovirus. A polyhistidine extension was incorporated at the C-terminus of the expressed protein, which, after purification of the protein on a nickel-agarose column, could be removed proteolytically by treatment with thrombin. Purified yields of P450 2D6 were 2.4 mg from 700 mL of cell culture. The protein had a greater than 90% heme content and was fully active, having no residual absorbance at 420 nm in the reduced CO complex. The quantities produced allowed direct study of the interaction of the substrate codeine with the enzyme by paramagnetic relaxation effects on the NMR spectrum of the substrate. Distances between the heme iron atom and substrate protons were calculated from these experiments, and the orientation of the substrate in the binding pocket was determined. This showed that codeine was bound with the methoxy group of the molecule closest to the heme iron (iron-methyl proton distance of 3.1 +/- 0.1 A), consistent with the observed O-demethylation to morphine. A model of the complex Of P450 2D6 with codeine was built from a multiple sequence and structure alignment of the known crystal structures for P450s, incorporating the experimental constraints derived from the NMR studies. This showed that the overall fold Of P450 2D6 is more similar to that of P450 BM3 than to either P450 cam or P450 terp. Codeine binds to P450 2D6 so that the methoxy group is directly above the A ring of the heme, while the basic nitrogen interacts with the carboxylate of aspartate 301.

Amino Acid Sequence↗

The intradermal effects of the H3 receptor agonist R alpha methylhistamine in human skin.

We have investigated the possible existence of the H3 histamine receptor in human skin with the highly selective ligands R alpha methylhistamine (RAMHA) (H3 agonist) and thioperamide (H3 antagonist). We compared the intradermal effects of RAMHA with histamine, and studied their potential modulation by the H1 antagonist terfenadine, and H2 antagonist cimetidine. The effects of RAMHA and thioperamide on codeine phosphate-, substance P- and histamine-induced weal and flare responses were also studied. RAMHA produced dose-related weal and flare responses that were approximately 10- and fivefold less, respectively, than responses to histamine. Flare responses to RAMHA were significantly inhibited by oral terfenadine (P < 0.05). Weal and flare responses to histamine after oral cimetidine showed much intersubject variation, and cimetidine did not significantly alter either RAMHA- or histamine-induced weal and flare responses. Codeine phosphate-, substance P- and histamine-induced responses were not significantly affected by concurrent administration of RAMHA. Thioperamide was not found to influence codeine phosphate-, substance P-, RAMHA- or histamine-induced effects. RAMHA induces vascular (weal and flare) responses in human skin, and these responses are partially inhibited by terfenadine. There is a trend for RAMHA to have an additive effect to the weal induced by substance P and histamine, although our results largely do not reach statistical significance. Thioperamide does not affect the vascular responses to RAMHA, codeine phosphate, histamine or substance P. We cannot conclude that the effects of RAMHA are induced by H3 receptors on cutaneous endothelial or mast cells.

Adult↗

Gas chromatographic/mass spectrometric detection of narcotine, papaverine, and thebaine in seeds of Papaver somniferum.

In addition to codeine and morphine, three more compounds: narcotine (noscapine), papaverine, and thebaine were found in Indian and Netherlands poppy seeds (Papaver somniferum L). The compounds were detected by a GC/MS technique and the identities were confirmed by comparing retention times and ion ratios with the known references. The concentrations of codeine, morphine, thebaine, papaverine, and narcotine were 44, 167, 41, 67, and 230 micrograms/g in Indian poppy seeds, and were 1.8, 39, 1.0, 0.17, 0.84 micrograms/g in Netherlands poppy seeds, respectively. Because these compounds may be urinary products after poppy seed consumption, the lowest detectable concentrations of codeine, morphine, thebaine, papaverine, and narcotine in urine are of interest and were found to be 4, 4, 5, 0.4, and 4 ng/ml, respectively. The detection of urinary narcotine, papaverine, or thebaine may be utilized to differentiate poppy seed consumption from illicit codeine, morphine, or heroin use.

Gas Chromatography-Mass Spectrometry↗

Diamorphine treatment for opiate dependence: putative markers of concomitant heroin misuse.

The supply of substitute opioid medication as a treatment for heroin dependence is now common practice. There is growing international interest in the prescription of injectable diamorphine for subgroups of patients who are unable to stop injecting opiate drugs; in the United Kingdom it is estimated that there are currently 300 patients prescribed diamorphine for this purpose. The detection of illicit heroin misuse (through urinary diamorphine metabolites) is confounded in subjects prescribed diamorphine. We investigated the potential to distinguish between the use of street heroin and pharmaceutical diamorphine through the detection in urine of various opiate alkaloids originating in the opium poppy, Papaver somniferum. Over a 7-week period, 532 clients of an urban substance misuse service provided a total of 1122 urine samples for clinical purposes. Using a novel mixed-mode solid-phase extraction and gas chromatography/mass spectrometry technique, we screened samples for morphine, 6-monoacetylmorphine, codeine, meconine, papaverine, noscapine, thebaine and their metabolites. All urine samples from diamorphine-treated patients were positive for morphine. Of samples from patients receiving other treatments, 30% (95%CI: 27-33%) were positive for morphine, indicating probable street heroin misuse. Of morphine-positive samples, 61% (95%CI: 55-67%), from the "other treatments" group were positive for at least one of codeine, meconine and putative noscapine or papaverine metabolites. This was reduced to 56% (95%CI: 50-62%) when excluding codeine. Only one sample (0.1%) was positive for any one of these putative markers in the absence of morphine, when excluding codeine. These findings show that the detection of urinary noscapine and papaverine metabolites is useful in distinguishing between use of pharmaceutical diamorphine and street heroin. This may be of benefit to promote safer and more effective prescribing of diamorphine in opiate dependency, and as an outcome measure in trials of diamorphine prescribing.

Journal Article↗

Testing human hair for drugs of abuse. III. Identification of heroin and 6-acetylmorphine as indicators of heroin use.

Hair samples from 20 documented heroin users contained 6-acetylmorphine, a unique metabolite of heroin, in all samples. Heroin was identified in smaller amounts in seven of these samples. The identity of 6-acetylmorphine and heroin was established by comparison of full scan spectra of extracts to standard reference materials. The presence of 6-acetylmorphine generally predominated over heroin, morphine, and codeine. The mean concentrations of analytes were as follows: 6-acetylmorphine, 0.90 ng/mg, N = 20; heroin, 0.17 ng/mg, N = 7; morphine, 0.26 ng/mg, N = 20; codeine, 0.18 ng/mg, N = 15. Analysis of hair samples obtained from 10 drug-free control subjects were negative for 6-acetylmorphine, morphine, and codeine. However, a small interfering peak was observed at the retention time for heroin. Control samples soaked in aqueous solutions of heroin and 6-acetylmorphine were found to be contaminated, even though an initial wash step was included in the analysis. These data suggest that hair analysis for 6-acetylmorphine can be used to differentiate heroin users from other types of opiate exposure (e.g., poppy seed, licit morphine, and codeine); however, environmental contamination can potentially produce false positives during opiate testing.

Adult↗

Diclofenac and ketorolac in the treatment of pain after photorefractive keratectomy.

BACKGROUND: Photorefractive keratectomy (PRK) can produce significant ocular pain. Topical diclofenac, a non-steroidal anti-inflammatory drug (NSAID), is effective in the reduction of this pain. This study compares a second NSAID, ketorolac, to diclofenac. METHODS: This prospective matched-control study involved 102 eyes of 102 patients. Prior to PRK, patients were randomly assigned to receive ketorolac or diclofenac drops. At the first postoperative visit, a standardized questionnaire was used to assess the patient's average and peak levels of discomfort. In addition, the quantities of acetaminophen and codeine consumed were recorded. RESULTS: The overall level of discomfort was 1.53 +/- 0.64 for diclofenac and 1.88 +/- 0.55 for ketorolac (scale: 0 to 4) (P = 0.004). The diclofenac group reported a peak discomfort level of 2.0 +/- 0.75 and the ketorolac group reported 2.3 +/- 0.62 (P > 0.05). The diclofenac group consumed 2000 +/- 1150 mg of acetaminophen and 92 +/- 54 mg of codeine whereas the ketorolac group consumed 2150 +/- 940 of acetaminophen and 98 +/- 50 mg of codeine (P > 0.05). CONCLUSIONS: The differences in levels of peak discomfort, acetaminophen ingestion, and codeine ingestion, were not statistically significant. As compared to ketorolac, diclofenac resulted in a statistically significant lower mean overall discomfort.

Administration, Topical↗

Comparison of the effects of two opioid antitussives, vadocaine hydrochloride, clobutinol and lidocaine on lung mechanics in guinea-pigs.

Intravenous administration of opioids, e.g. morphine and codeine, causes bronchoconstriction in animals and susceptible patients such as asthmatics. Therefore, the effects of two opioid antitussives (codeine and dextromethorphan), two non-opioid antitussives (vadocaine hydrochloride (2',4'-dimethyl-6'-methoxy-3-(2-methylpiperidyl) propionanilide hydrochloride, OR K-242-HCl; INN: vadocaine) and clobutinol), and lidocaine on basal lung mechanics and methacholine (MeCh, 6 micrograms/kg i.v.)-induced airway obstruction were investigated in anaesthetized guinea-pigs. Intravenous administration of codeine (10-20 mg/kg) produced a dual response in the airways; initial bronchoconstriction was followed by attenuation of the MeCh-response. Dextromethorphan (10 and 15 mg/kg) caused bronchoconstriction only. Both the opioids affected dynamic lung compliance (CDyn) more than lung resistance (RL). At doses between 1 and 20 mg/kg i.v., vadocaine, clobutinol, and lidocaine had no obvious effect on the airways. Dextromethorphan and vadocaine, both at doses of 10 and 15 mg/kg, and clobutinol (15 and 20 mg/kg) caused irreversible bradycardia and hypotension, whereas codeine (5-20 mg/kg) increased blood pressure, and to a lesser extent heart rate. These results suggest that intravenous administration of an opioid antitussive influences the small peripheral airways more than the large airways, whether the opioid has euphoric analgesic properties or not. In contrast to this, non-opioid antitussives such as vadocaine and clobutinol are without effect. At large doses, all antitussives influence the cardiovascular system considerably.

Amino Alcohols↗